A conventional method for allowing crystals of paroxetine hydrochloride ½-hydrate to separate out with a polar organic solvent such as a lower alcohol, which contains water or no water, is a method for crystallization with 2-propanol containing 10% of water as a solvent (see, for instance, International Journal of Pharmaceutics, 42 (1988), 135-143 (p. 136, left column, the first paragraph)). Also, there is a method for crystallization by recrystallizing paroxetine hydrochloride using IMS (industrial methanol) as a solvent for recrystallization (see, for instance, Example 3(a) in EP 223403 B1 corresponding to JP-B-6-47587; and Example 4(a) of UK Patent Application No. 8526407). Also, there are some examples in which only water is used as a solvent for crystallization without using a polar organic solvent (see, for instance, Examples 2 and 3(b) in EP 223403 B1; and Examples 3 and 4(b) in UK Patent Application No. 8526407).
In addition, an attempt to solve a problem of coloration in pink with paroxetine hydrochloride was made in WO 02/102382, which was laid open to public inspection after the priority date of the present application. In this method, when paroxetine hydrochloride is prepared by a reaction of a paroxetine base with HCl, HCl is used in an amount of less than 1 mole equivalent or in such an amount that the pH becomes about 3 to about 8, due to a disadvantage that, for instance, impurities are produced when HCl (pH: at most 1) is used in a small excess amount. As Far as the present inventors know, toluene which is a non-polar solvent has been used as a solvent for the preparation of paroxetine hydrochloride in the existence of a small excess amount of HCl (see EP 223403 B1 and UK Patent Application No. 8526407).